The disclosure relates generally to the field of alleviating headaches and other head pain.
The human central nervous system (CNS; i.e., the brain and spinal cord) are surrounded by three membranous structures, the distal structure designated the dura mater, the proximal structure designated the pia mater, and the arachnoid (or “arachnoid mater”) being interposed between these two. The subarachnoid space (i.e., the cavity between the arachnoid and the enclosed CNS components) is filled with a liquid designated cerebrospinal fluid (CSF). CSF also fills the ventricles of the brain and the central canal of the spinal cord.
CSF is a liquid that is normally clear in healthy individuals. In addition to supporting and cushioning the CNS from physical trauma, CSF can serve as a medium for transport of nutrients, metabolites, or other compounds across the blood-brain barrier.
There is a natural flow of CSF that is attributable to production of CSF (primarily by choroid plexus tissues, with lesser production at cerebral vascular and ventricular surfaces), migration therefrom through brain ventricles, across brain and spinal cord surfaces through the subarachnoid space, and reabsorption into the bloodstream through arachnoid granulations and lymphatic channels. Although the rate of CSF formation appears to vary among individuals, production rates on the order of 500 milliliters per day are not unusual. The volume of CSF-filled space within the CNS of a normal, healthy individual is on the order of about 135-150 milliliters, indicating that the normal daily turnover of CSF in the CNS of a normal, healthy individual is roughly 3-4 times per day.
CSF can be accessed by a variety of known techniques, among the most common of which is lumbar puncture (LP). In LP procedures, the tip of a needle is inserted into the subarachnoid space in the spinal column, typically between the L3 and L4 vertebrae or between the L4 and L5 vertebrae (i.e., to avoid contact between the needle and the spinal cord, which typically does not extend to these positions). The subarachnoid space can thus be accessed by way of the lumen of the needle, CSF can be withdrawn through the lumen, or liquid can be introduced into the subarachnoid space to mix with or displace CSF.
The subarachnoid space usually exists in a hyperpressurized state, relative to the extracorporeal atmosphere, meaning that if a channel is opened between the subarachnoid space and the outside of the body (e.g., via a LP needle having no flow regulator), CSF will initially flow from the subarachnoid space to the exterior of the body until the pressure within the subarachnoid space substantially equals the extracorporeal pressure. The pressure difference between the subarachnoid space and the extracorporeal atmosphere (the “intracranial pressure;” ICP) is typically on the order of about 20 centimeters of water (cmW; i.e., about 15 millimeter of mercury, mmHg) or less in a normal, non-diseased prone human at rest. Methods of assessing ICP are well known and include, for example, discrete manometric measurements made by way of LP and use of implanted ICP sensors.
In the past, others have recognized that abnormally high ICP (i.e., >25 cmW) can lead to or cause head pain and, if the abnormally high ICP is of sufficient duration and severity, it can result in serious or fatal brain damage. Common causes of abnormally high ICP include head trauma (especially that inducing cerebral edema or formation of intracranial heniatoma), intracranial tumor occurrence, infections such as meningitides, and hydrocephalus. Owing to the importance of relieving abnormally high ICP when it occurs, a variety of agents and techniques have been developed for reducing ICP.
A simple method of reducing ICP is simply draining CSF from the subarachnoid space, such as by way of a LP needle or a catheter (an “extraventricular drain”) extending into a brain ventricle. Another physical methods of reducing localized ICP is installation of a shunt within the subarachnoid space (e.g., in instances in which CSF produced within a particular cerebral ventricle is constrained by abnormal CNS anatomical structure from normal flow through the subarachnoid space). Numerous devices suitable for draining CSF from the subarachnoid space are known, including devices generally designated “cerebral shunts” (e.g. ventriculoperitoneal shunts) and devices (e.g., lumboperitoneal shunts) intended for draining CSF from portions of the spinal column. Other fenestration methods for facilitating drainage of fluid from a tissue-delineated compartment are known, such as the AQUAFLOW brand collagen glaucoma drainage device (STAAR Surgical, Monrovia, Calif.), which has the ability to facilitate flow of intraocular fluid from beneath the cornea to the exterior of the eye (i.e., thereby relieving and preventing abnormally high intraocular pressure). Other known methods involve fenestration of the dura mater, such as optic nerve sheath decompression surgical techniques.
Numerous pharmaceutical agents are known to decrease the rate of CSF production, and use of such agents to reduce abnormally high ICP is known. Examples of such agents include acetazolamide (e.g., acetazolamide sold under the registered trademark DIAMOX, which trademark is owned by American Cyanamid Company, New York, N.Y.), topiramate (e.g., topiramate sold under the registered trademark TOPAMAX, which trademark is owned by Johnson & Johnson, New Brunswick, N.J.) and other known inhibitors of carbonic anhydrase, including methazolamide, dorzolamide (TRUSOPT, a registered trademark of Merck & Co., Inc., Whitehouse Station, N.J.). Furthermore, other agents are known to reduce the volume of CSF in human patients, including diuretics (e.g., bumetanide and furosemide).
Normal pressure hydrocephalus (normotensive hydrocephalus) is a condition in which ICP is not abnormally high (normotensive hydrocephalus patients often exhibit ICP of 15-20 cmW). Normotensive hydrocephalus patients usually exhibit urinary incontinence, gait anamolies, and dementia, but do not exhibit the classic hydrocephalus symptoms of headache, nausea, and vomiting. Brain ventricles are typically abnormally enlarged in normotensive hydrocephalus.
Head pain is a common occurrence and is symptomatic of a wide variety of physiological states, including many human diseases and disorders. Head pain can be attributable, for example, to trauma to the head or other body parts, migraine and other cerebroneurovascular disorders, stress and muscle tension, infections, sensitivity to chemicals, and many other causes. One particular type of headache is known to be associated with disruption of CSF homeostasis—so-called post dural puncture headache (PDPH). PDPH is attributable to loss of CSF through a puncture of the dura matter, such as occurs in the LP procedure. In PDPH, loss of CSF through the dural puncture site is believed to reduce the brain-protecting capacity of durally-retained CSF, leading to CNS-irritating traction between CNS components and their associated meninges which is experienced by the patient as head pain. PDPH can be treated by methods involving sealing of the puncture site, which results in increased volume and pressure of CSF.
It is common that the etiology of head pain (especially chronic head pain) cannot be determined from simple reports and examination of human patients. As a result, numerous treatment modalities are sometimes attempted, in the hope that one modality provides relief. Furthermore, there are patients for whom no previously known treatment modalities provide relief from their chronic head pain.
A need exists for additional methods of assessing and treating head pain, especially chronic head pain of previously inexplicable etiology. The present disclosure relates to such methods.